Management of Gout

Publication Date: May 20, 2020
Last Updated: April 13, 2022

Recommendations

Indications for pharmacologic urate-lowering therapy (ULT)

For patients with 1 or more subcutaneous tophi, we strongly recommend initiating ULT over no ULT. (High-quality evidence, Strong recommendation)
608
For patients with radiographic damage (any modality) attributable to gout, we strongly recommend initiating ULT over no ULT. (Moderate-quality evidence, Strong recommendation)
608
For patients with frequent gout flares (>2/year), we strongly recommend initiating ULT over no ULT. (High-quality evidence, Strong recommendation)
608
For patients who have previously experienced >1 flare but have infrequent flares (<2/year), we conditionally recommend initiating ULT over no ULT. (Moderate-quality evidence, Conditional recommendation)
608
For patients experiencing their first flare, we conditionally recommend against initiating ULT over no ULT, with the following exceptions. (Moderate-quality evidence, Conditional recommendation)
608
For patients experiencing their first flare and CKD stage >3, SU >9 mg/dl, or urolithiasis, we conditionally recommend initiating ULT. (Very low-quality evidence, Conditional recommendation)
608
For patients experiencing their first flare and CKD stage >3, SU >9 mg/dl, or urolithiasis, we conditionally recommend initiating ULT. (High-quality evidence, Conditional recommendation)
  • There is randomized clinical trial data to support the benefit that ULT lowers the proportion of patients who develop incident gout. However, based on the attributable risk, 24 patients would need to be treated for 3 years to prevent a single (incident) gout flare leading to the recommendation against initiating ULT in this patient group.
608

Recommendations for choice of initial urate-lowering therapy (ULT) in patients with gout

For patients starting any ULT, we strongly recommend allopurinol over all other ULT as the preferred first-line agent for all patients, including in those with CKD stage >3. (Moderate-quality evidence, Strong recommendation)
608
We strongly recommend a xanthine oxidase inhibitor over probenecid for those with CKD stage >3. (Moderate-quality evidence, Strong recommendation)
608
For allopurinol and febuxostat, we strongly recommend starting at a low dose with subsequent dose titration to target over starting at a higher dose (e.g., <100 mg/day [and lower in patients with CKD] for allopurinol or <40 mg/day for febuxostat). (Moderate-quality evidence, Strong recommendation)
608
For probenecid, we conditionally recommend starting at a low dose (500 mg once or twice daily) with dose titration over starting at a higher dose. (Moderate-quality evidence, Conditional recommendation)
608
We strongly recommend initiating concomitant antiinflammatory prophylaxis therapy (e.g., colchicine, NSAIDs, prednisone/prednisolone) over no antiinflammatory prophylaxis. (Moderate-quality evidence, Strong recommendation)
  • The choice of specific antiinflammatory prophylaxis should be based upon patient factors.
608
We strongly recommend continuing prophylaxis for 3–6 months rather than <3 months, with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience flares. (Moderate-quality evidence, Strong recommendation)
608
When the decision is made that ULT is indicated while the patient is experiencing a gout flare, we conditionally recommend starting ULT during the gout flare over starting ULT after the gout flare has resolved. (Moderate-quality evidence, Conditional recommendation)
608
We strongly recommend against pegloticase as first-line therapy. (Moderate-quality evidence, Strong recommendation)
  • Moderate evidence is in support of the efficacy of pegloticase, but due to cost, safety concerns, and favorable benefit-to-harm ratios of other untried treatment options, the recommendation is against using pegloticase as first-line agent.
608

Recommendations for all patients taking urate-lowering therapy (ULT)

For all patients taking ULT, we strongly recommend a treat-to-target strategy of ULT dose management that includes dose titration and subsequent dosing guided by serial SU values to achieve an SU target over a fixed, standard-dose ULT strategy. (Moderate-quality evidence, Strong recommendation)
608
For all patients taking ULT, we strongly recommend continuing ULT to achieve and maintain an SU target of <6 mg/dl over no target. (High-quality evidence, Strong recommendation)
608
For all patients taking ULT, we conditionally recommend delivery of an augmented protocol of ULT dose management by nonphysician providers to optimize the treat-to-target strategy that includes patient education, shared decision-making, and treat-to-target protocol. (Moderate-quality evidence, Conditional recommendation)
608
We conditionally recommend continuing ULT indefinitely over stopping ULT. (Very low-quality evidence, Conditional recommendation)
608

Recommendations for patients taking specific urate-lowering therapy (ULT) medications

Allopurinol

We conditionally recommend testing HLA–B*5801 prior to starting allopurinol for patients of Southeast Asian descent (e.g., Han Chinese, Korean, Thai) and African American patients, who have a higher prevalence of HLA–B*5801. (Very low-quality evidence, Conditional recommendation)
608
We conditionally recommend against HLA–B*5801 testing in all others. (Very low-quality evidence, Conditional recommendation)
608
For patients with a prior allergic response to allopurinol who cannot be treated with other oral ULT, we conditionally recommend using allopurinol desensitization. (Very low-quality evidence, Conditional recommendation)
608

Febuxostat

For patients with gout taking febuxostat with a history of CVD or a new CV event, we conditionally recommend switching to an alternative ULT agent if available and consistent with other recommendations in this guideline. (Moderate-quality evidence, Conditional recommendation)
608

Uricosurics

For patients considered for, or taking uricosuric treatment, prior to starting any uricosuric treatment, we conditionally recommend against checking urinary uric acid over checking urinary uric acid. (Very low-quality evidence, Conditional recommendation)
608
For patients taking uricosuric treatment, we conditionally recommend against alkalinizing urine. (Very low-quality evidence, Conditional recommendation)
608

When to consider switching to a new urate-lowering therapy (ULT) strategy

For patients with gout taking their first XOI monotherapy at maximum-tolerated or FDA-indicated dose who are not at SU target and/or have continued frequent gout flares or nonresolving subcutaneous tophi, we conditionally recommend switching the first XOI to an alternate XOI agent over adding a uricosuric agent. (Very low-quality evidence, Conditional recommendation)
608
For patients with gout where XOI, uricosurics, and other interventions have failed to achieve SU target and who have frequent gout flares or nonresolving subcutaneous tophi, we strongly recommend switching to pegloticase over continuing current ULT. (Moderate-quality evidence, Strong recommendation)
  • There is moderate certainty of evidence about the efficacy of the benefits, harms, and high certainty about the costs of pegloticase. For patients with high disease activity, the magnitude of potential benefits outweighs the harms and costs of the drug.
608
For patients with gout for whom XOI, uricosurics, and other interventions have failed to achieve serum urate target and who have infrequent gout flares (<2 flares/year) and no tophi, we strongly recommend against switching to pegloticase over continuing current ULT. (Moderate-quality evidence, Strong recommendation)
  • For patients with minimal disease activity, the smaller potential benefits do not outweigh the harms and costs of the drug.
608

Gout flare management

For patients experiencing a gout flare, we strongly recommend using oral colchicine, NSAIDs, or glucocorticoids (oral, intraarticular, or intramuscular) as appropriate first-line therapy for gout flares over IL-1 inhibitors or ACTH (the choice of colchicine, NSAIDs, or glucocorticoids should be made based on patient factors and preferences). (High-quality evidence, Strong recommendation)
  • High quality of evidence from network meta-analyses supporting canakinumab, which has superior mean pain score reduction and mean day-2 joint tenderness reduction. However, the Voting Panel raised concern that the comparator was weak (triamcinolone 40 mg) and that cost issues significantly favor other agents.
608
For patients experiencing a gout flare for whom other antiinflammatory therapies are poorly tolerated or contraindicated, we conditionally recommend using IL-1 inhibition over no therapy (beyond supportive/ analgesic treatment). (Moderate-quality evidence, Conditional recommendation)
608
For patients who may receive NPO, we strongly recommend glucocorticoids (intramuscular, intravenous, or intraarticular) over IL-1 inhibitors or ACTH. (High-quality evidence, Strong recommendation)
  • High quality of evidence from network meta-analyses supporting canakinumab, which has superior mean pain score reduction and mean day-2 joint tenderness reduction. However, the Voting Panel raised concern that the comparator was weak (triamcinolone 40 mg) and that cost issues significantly favor other agents.
608

Management of lifestyle factors

For patients with gout, regardless of disease activity, we conditionally recommend limiting alcohol intake. (Low-quality evidence, Conditional recommendation)
608
For patients with gout, regardless of disease activity, we conditionally recommend limiting purine intake. (Low-quality evidence, Conditional recommendation)
608
For patients with gout, regardless of disease activity, we conditionally recommend limiting purine intake. (Very low-quality evidence, Conditional recommendation)
608
For overweight/obese patients with gout, regardless of disease activity, we conditionally recommend weight loss. (Very low-quality evidence, Conditional recommendation)
608
For patients with gout, regardless of disease activity, we conditionally recommend against adding vitamin C supplementation. (Low-quality evidence, Conditional recommendation)
608

Management of concurrent medications

For patients with gout, regardless of disease activity, we conditionally recommend switching hydrochlorothiazide to an alternate antihypertensive when feasible. (Very low-quality evidence, Conditional recommendation)
608
We conditionally recommend choosing losartan preferentially as an antihypertensive when feasible. (Very low-quality evidence, Conditional recommendation)
608
We conditionally recommend against stopping low-dose aspirin (in those who are taking this medication for appropriate indications). (Very low-quality evidence, Conditional recommendation)
608
We conditionally recommend against adding or switching to fenofibrate. (Very low-quality evidence, Conditional recommendation)
608

Recommendation Grading

Overview

Title

Management of Gout

Authoring Organization

Publication Month/Year

May 20, 2020

Last Updated Month/Year

February 6, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory

Intended Users

Nurse, nurse practitioner, physician, physician assistant, podiatrist

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D006073 - Gout, D015210 - Arthritis, Gouty

Keywords

gout, tophaceous gout, acute gout

Supplemental Methodology Resources

Data Supplement